Molecular self-assembly with scaffolded deoxyribonucleic acid (DNA) origami enables arranging many thousand nucleotides with subnanometer precision at specified locations in space to yield custom-shaped objects with dimensions on the scale of 1 to 1000 nanometers (1 nanometer, nm, =10−9 meters). [See Rothemund, P W K. “Folding DNA to create nanoscale shapes and patterns.”, Nature, 440, 297-302, (2006); Lulu, Q., Ying, W., Zhao, Z., Jian, Z., Dun, P., Yi, Z., Qiang, L., Chunhai, F., Jun, H., Lin, H. “Analogic China map constructed by DNA”, Chinese Sci Bull, 51, 2973-2976, (2006); Douglas, S M., Chou, J J., Shih, W M. “DNA-nanotube-induced alignment of membrane proteins for NMR structure determination”, Proc Natl Acad Sci U.S.A., 104, 6644-6648, (2007); Andersen, E S., Dong, M., Nielsen, M M., Jahn, K., Lind-Thomsen, A., Mamdouh, W., Gothelf, K V., Besenbacher, F., Kjems, J. “DNA origami design of dolphin-shaped structures with flexible tails”, ACS Nano, 2, 1213-1218, (2008); Ke Y., Sharma, J., Liu, M., Jahn, K., Liu, Y., Yan, H. “Scaffolded DNA origami of a DNA tetrahedron molecular container”, Nano Lett, 9, 2445-2447, (2009); Andersen, E S., Dong, M., Nielsen, M M., Jahn, K. Subramani, R. Mamdouh, W., Golas, M M., Sander, B., Stark, H., Oliveira, C L P., Pedersen, J S., Birkedal, V., Besenbacher, F., Gothelf, K V., Kjems, J. “Self-assembly of a nanoscale DNA box with a controllable lid”, Nature, 459, 73-76, (2009); Douglas, S M., Dietz, H., Liedl, T., Högberg, B., Graf, F., Shih, W M. “Self-assembly of DNA into nanoscale three-dimensional shapes.”, Nature, 459, 414-418, (2009); Dietz, H., Douglas, S M., Shih, W M. “Folding DNA into twisted and curved nanoscale shapes.”, Science, 325, 725-730, (2009); Douglas, S M., Marblestone, A H., Teerapittayanon, S., Vazquez, A., Church, G M., Shih, W M. “Rapid prototyping of 3D DNA-origami shapes with caDNAno”, Nucleic Acids Res, 37, 5001-5006, (2009) Ke, Y., Douglas, S M., Liu, M., Sharma, J., Cheng, A., Leung, A., Liu, Y., Shih, W M., Yan, H. “Multi-layer DNA origami packed on a square lattice”, J Am Chem Soc, 131, 15903-15908, (2009); Pound, E., Ashton, J R., Becerril, H A., Woolley, A T. “Polymerase chain reaction based scaffold preparation for the production of thin, branched DNA origami nanostructures of arbitrary sizes.”, Nano Lett, 9, 4302-4305, (2009); Endo, M., Hidaka, K., Kato, T., Namba, K., Sugiyama, H. “DNA prism structures constructed by folding of multiple rectangular arms”, J Am Chem Soc, 131, 15570-15571, (2009); Kuzuya, A., Komiyama, M. “Design and construction of a box-shaped 3D-DNA origami.”, Chem Commun (Camb), 4182-4184, (2009); Liedl, T., Högberg, B., Tytell, J., Ingber, D E., Shih, W M. “Self-assembly of three-dimensional prestressed tensegrity structures from DNA”, Nat Nanotechnol, 5, 520-524, (2010); for which the entire contents of each are hereby incorporated as if fully set forth herein, except as the terminology is inconsistent with the terminology used elsewhere herein].
DNA origami entails folding a single-stranded ‘scaffold’ DNA molecule up to several thousand bases long into custom-shaped single-layer or multi-layer bundles of B-form DNA double helices with the help of a set of short (<60 bases) single-stranded ‘staple’ oligonucleotides that are currently derived from chemical synthesis. DNA origami objects can be designed in a few hours with the help of software developed specifically for this purpose, and the manual labor required for setting up assembly reactions and purification is limited to handling a multi-channel pipette and running agarose gels. A rich diversity of shapes has been built so far with scaffolded DNA origami. A comprehensive review has recently been published in Shih, W M., Lin, C. “Knitting complex weaves with DNA origami”, Curr Opin Struct Biol, 20, 276-282, (2010) the entire contents of which are hereby incorporated as if fully set forth herein, except as the terminology is inconsistent with the terminology used elsewhere herein.
Scaffolded DNA origami enables the programmable synthesis of complex nanoscale structures with a broad range of potential scientific and industrial applications. However, the rational design of DNA origami structures to target specifications is currently limited by a lack of quantitative tools for predicting the solution shape and mechanical integrity of designed structures, and using these predictive capabilities for unsupervised, automated design.